The major histocompatibility complex (MHC) is a highly polymorphic region of the genome in diverse vertebrate groups, such as guppies, geckos, pheasants, alligators, and humans. However, more than 50 years after the MHC's initial description, the mechanisms maintaining such diversity are still not clearly understood. Competing hypothesis include 1) selection for pathogen resistance, acting through heterozygote or rare-allele advantage, 2) selection for maternal-fetal incompatibility, acting through genetic or immunological means, and 3) selection for inbreeding avoidance, acting through mate choice or fetal loss. This proposal will evaluate the latter two mechanisms, namely the effects of MHC genes on mate choice and subsequent reproductive fitness in a large, well-documented zoo population of Peromyscus polionotus, the old field mouse. MHC loci will be PCR- amplified using P. maniculatus or leucopus MHC class I and II primers and allelic variation assessed by SSCP analysis and direct sequencing. MHC- gene effects on mate choice will be evaluated by comparing MHC differences at the allelic, amino acid, or nucleotide level between "chosen" and "unchosen" partners. Reproductive performance will be assessed in MHC- similar and dissimilar "paired" mates. P. polionotus is a genus known to exhibit both kin recognition and mate choice. Also, P. polionotus mates monogamously for life, so choice of a quality ate should be important for individual fitness. However, the cue used for kin identification and mate choice in P. polionotus is unknown. The study will examine if MHC-derived cues are used for kin recognition in Peromyscus species, and especially P. polionotus, and will also help evaluate two potential selective factors that may maintain MHC diversity: mate choice and reproductive success.